Abdominal aortic aneurysm (AAA) can lead to death from rupture and exsanguinating hemorrhage. AAA afflicts 2-4% of U.S. adults, and rupture accounts for 1-2% of deaths in men >65 years of age. Overall, AAA rupture is the 13th leading cause of death in the US. Surgical repair prevents rupture, but both open and endovascular repairs leave the aneurysm behind, largely intact. After repair, patients demonstrate reduced fitness and a higher death rate than the general population. We showed that 60% of 505 AAA patients suffer from sarcopenia (low muscle mass) at surgery. Furthermore, AFTER repair, sarcopenic AAA patients suffer a 40% 5-year mortality, a death rate twice that of non-sarcopenic AAA patients and similar to that of node-positive colon cancer. As well, we find that AAA patients with myosteatosis?fatty infiltration of muscle?also suffer increased 5-year mortality. Thus, both muscle mass and quality predict death after AAA repair. AAA-associated sarcopenia and cancer-associated muscle wasting (known as cachexia) demonstrate similarities. Cancer cachexia reduces function, quality, and length of life. Patients and mice with cancer cachexia and those with AAA both exhibit increased circulating inflammatory cytokines. Moreover, much like cachexia-inducing tumors, aneurysms demonstrate reactive stroma, infiltrating immune cells, and expression of inflammatory cytokines. Certain of these cytokines (e.g. IL- 6) are clearly causative of cancer-induced cachexia and their specific blockade has been trialed to reduce cancer cachexia, while other cytokines are under study. In general, in cachexia cardiac muscle and function are affected along with skeletal muscle mass and function. We hypothesize that AAA, like certain tumors and other non-healing wounds, induces loss of cardiac and skeletal muscle quality, function, and mass, a.k.a cachexia, through chronic inflammation. Repair of the aneurysm eliminates death by rupture, but the remnant aneurysm sustains inflammation, resulting in progressive weakness, functional decline, and death. If so, current AAA therapies that buttress the aneurismal segment palliate, but do not cure. Definitive treatment would remove the source of inflammation?the aneurysm?or treat the hyperinflammatory state. This is a paradigm shift in framing the morbidity and mortality of AAA. We will investigate this hypothesis both in AAA patients and in mouse models. Here we will define temporal changes in body composition, heart and skeletal muscle mass, function and quality; identify cachexia activity in plasma and blood cells; profile pathways in key tissues; and validate AAA models for further pre-clinical testing. This could transform our understanding of mechanisms of death and disability in AAA and lead to improvements in treatment approach.